The development of a highly accurate, blood-based pancreatic adenocarcinoma screen that would be accurate enough to test the general population for this deadly disease may not be far out of reach, according to data presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, being held here June 18-21, 2012.
Matthew Firpo, Ph.D., a research assistant professor at the Huntsman Cancer Institute at the University of Utah, came to the conclusion that screening a panel of biomarkers might be effective by embracing the idea that pancreatic adenocarcinoma has vast genetic heterogeneity, meaning no single biomarker exists that is strongly correlated with its diagnosis across the population of people who develop the disease.
Although it is widely accepted that earlier detection of pancreatic adenocarcinoma would improve survival outcomes, research efforts to date have been unsuccessful at identifying a biomarker or biomarker panel that has a high diagnostic sensitivity.
“Any tool that we deploy in the general population to screen for this disease would have to be very accurate,” Firpo explained. “Because this cancer is rare, if everyone older than age 50 in the United States was screened with a test that was only 95 percent accurate, we would have more than three million people each year with a false positive identification of pancreatic adenocarcinoma.”
Therefore, Firpo said that any test for pancreatic adenocarcinoma deployed to the general population must have an accuracy of greater than 99 percent. To see if such levels of accuracy were possible, the researchers measured the levels of nine biomarkers of pancreatic adenocarcinoma in the blood of 117 healthy control participants, 58 participants with chronic pancreatitis and 159 patients with pancreatic adenocarcinoma.
Using a statistical model, they determined that many of these weak biomarkers present in those patients with pancreatic adenocarcinoma had 95 percent specificity for the disease, but, on average, only a 32 percent sensitivity.
“Based on the data, and specifying 99 percent specificity, it would take a panel of 40 biomarkers with 32 percent average sensitivity each and 95 percent specificity, of which seven biomarkers were above this threshold,” Firpo said.
The key to the study, according to Firpo, is accepting the fact that pancreatic adenocarcinomas are genetically heterogeneous. By developing a model that accounted for the heterogeneity they were able to get over 99 percent accuracy.
“Identifying 40 biomarkers is reasonable. We believe we can find 40 biomarkers that are weak classifiers of the disease,” he said. “That means that based on the current understanding of biomarkers that we have, there is hope for developing a panel that would have greater than 99 percent accuracy.”
Firpo said that the next step is to systematically identify 40 to 50 biomarkers that have these characteristics – 32 percent sensitivity and 95 percent specificity – or better.
Abstract: Prospects for developing a biomarker panel for accurate detection of pancreatic adenocarcinoma. Matthew A. Firpo, Kenneth M. Boucher, Sean J. Mulvihill. University of Utah, Salt Lake City, UT
American Association for Cancer Research